P1683: PERSISTENT HYPERCOAGULABILITY, ENDOTHELIOPATHY AND INFLAMMATION IN COVID-19 PATIENTS APPROXIMATING 1 YEAR AFTER RECOVERY.
Authors: B. E. Fan, S. W. Wong, C. L. L. Sum, G. H. Lim, B. P. Leung, R. Dalan, B. E. Young, D. C. Lye, C. Cheung, K. Ramanathan, C. W. Tan, E. S. Yap, Y. W. Chia
Journal: HemaSphere (2022)

Background: Sustained hypercoagulability and endotheliopathy has been demonstrated in convalescent COVID-19 patients for up to 4 months from recovery in previous studies. Aims: We performed a prospective, observational study assessing for hypercoagulability, endotheliopathy and inflammation in recovered COVID-19 patients beyond 6 months of recovery. Methods: The haemostatic (coagulation tests, global haemostatic tests), endothelial function and inflammatory profiles of recovered COVID-19 patients were evaluated at least 6 months after diagnosis of COVID-19. 39 patients were reviewed at a mean of 12.7±3.6 months following recovery from SARS-CoV-2 infection. These values were compared with a control group of healthy volunteers (n=124) who did not have COVID-19. Results: Among the 39 patients (71.8% males, median age 43 years, 11 having asymptomatic COVID-19, 19 having mild to moderate COVID-19, 2 having severe COVID-19 and 7 having critical COVID-19 requiring ICU care), 2 patients had pulmonary embolism during acute SARS-CoV-2 infection, and 1 patient without cardiovascular risk factors had post COVID-19 acute ischaemic limb. COVID-19 patients had significantly higher biomarkers of hypercoagulability, endothelial dysfunction and inflammation as compared to controls (Figure 1). Elevated D-dimer and Factor VIII levels above the normal ranges were noted in 17.9% (7/39) and 48.7% (19/39) of COVID-19 patients respectively, with a higher median D-dimer 0.34 μg/mL (IQR 0.28, 0.46) (p < 0.001) and Factor VIII 150% (IQR 171, 203) (p=0.004), compared to controls. Thrombin generation (Thromboscreen) also showed higher median endogenous thrombin potential (ETP) 1352nM*min (IQR 1152, 1490)(p=0.002), peak height 221.4nM (IQR 170.2, 280.4)(p=0.01) and a delayed lag time 2.4min (1.42-2.97)(p=0.0002) compared to controls. Raised endothelial biomarkers such as von Willebrand factor antigen (VWF:Ag) and ICAM-1 were observed in 17.9% (7/39) and 7.7% (3/39) of COVID-19 patients respectively, with a higher median VWF:Ag 117%(IQR 86, 154)(p=0.02) and ICAM-1 54.1%(IQR 43.8, 64.1)(p=0.004) than controls. Interleukin-6 (IL-6) was noted to be raised in 35.9% (14/39) of recovered COVID-19 patients, with a higher median IL-6 of 1.5pg/ml (IQR 0.6, 3.0) compared to controls. Subgroup analysis stratifying COVID-19 patients by age (≥50 years old), COVID-19 mRNA vaccination before acquiring SARS-CoV-2 infection, or pre-existing cardiovascular risk factors did not show any statistically significant differences across haemostatic, endothelial or inflammatory parameters. Patients who had experienced mild or asymptomatic COVID-19 compared with moderate to severe COVID-19 also demonstrated raised markers of hypercoagulability, endothelial dysfunction and inflammation. Image:Summary/Conclusion: Persistent hypercoagulability, endotheliopathy and inflammation is still detectable approximately 1 year from recovery in COVID-19 patients, with prior COVID-19 mRNA vaccination not appearing to reduce this risk.